Author | Tibúrcio, Rafael | |
Author | Narendran, Gopalan | |
Author | Barreto-Duarte, Beatriz | |
Author | Queiroz, Artur T L | |
Author | Araújo-Pereira, Mariana | |
Author | Anbalagan, Selvaraj | |
Author | Nayak, Kaustuv | |
Author | Ravichandran, Narayanan | |
Author | Subramani, Rajasekaran | |
Author | Antonelli, Lis Ribeiro do Valle | |
Author | Satagopan, Kumar | |
Author | Anbalagan, Komathi | |
Author | Porter, Brian O | |
Author | Sher, Alan | |
Author | Swaminathan, Soumya | |
Author | Sereti, Irini | |
Author | Andrade, Bruno B | |
Access date | 2023-03-20T15:39:53Z | |
Available date | 2023-03-20T15:39:53Z | |
Document date | 2022 | |
Citation | TIBÚRCIO, Rafael et al. Frequency of CXCR3+ CD8+ T-Lymphocyte Subsets in Peripheral Blood Is Associated With the Risk of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Development in Advanced HIV Disease. Front Immunol., v. 13, 873985, 2022. doi: 10.3389/fimmu.2022.873985. | en_US |
ISSN | 1664-3224 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/57459 | |
Language | eng | en_US |
Publisher | Frontiers Research Foundation | en_US |
Rights | open access | en_US |
Title | Frequency of CXCR3(+) CD8(+) T-Lymphocyte Subsets in Peripheral Blood Is Associated With the Risk of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Development in Advanced HIV Disease | en_US |
Type | Article | en_US |
Abstract | Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4+ T cell-derived IFN-γ. Nevertheless, the possible participation of CD8+ T cells in TB-IRIS development remains unclear.
Methods: We performed a comprehensive assessment of the composition of CD8+ T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART.
Results: We found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8+ T cells during the onset of IRIS and that the levels of these cells positively correlate with baseline mycobacterial smear grade. TB-IRIS individuals exhibited higher frequencies of effector memory and lower percentages of naïve CD8+ T cells than their Non-IRIS counterparts. In both TB-IRIS and Non-IRIS patients, ART commencement was associated with fewer significant correlations among memory CD8+ T cells and cells from other immune compartments. Networks analysis revealed distinct patterns of correlation between each memory subset with inflammatory cytokines suggesting different dynamics of CD8+ T cell memory subsets reconstitution. TB-IRIS patients displayed lower levels of memory cells positive for CXCR3 (a chemokine receptor that plays a role in trafficking activated CD8+ T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3+ naïve CD8+ T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3+ effector CD8+ T cells were positively associated with the probability of TB-IRIS development.
Conclusion: Our data suggest that TB-IRIS individuals display a distinct profile of memory CD8+ T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3+ CD8+ T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8+ T cells in TB-IRIS pathophysiology. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brazil/Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil/Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brazil. | en_US |
Affilliation | Department of Clinical Research. National Institute for Research in Tuberculosis. Chennai, India. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brazil/Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil/ Universidade Salvador. Curso de Medicina. Salvador, BA, Brazil/Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação em Clínica Médica. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil/Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Center of Data and Knowledge Integration for Health. Salvador, BA, Brazil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brazil/Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil/Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brazil. | en_US |
Affilliation | Department of Clinical Research. National Institute for Research in Tuberculosis. Chennai, India. | en_US |
Affilliation | Department of Clinical Research. National Institute for Research in Tuberculosis. Chennai, India/ICGEB-Emory Vaccine Centre. International Centre for Genetic Engineering and Biotechnology. New Delhi, India. | en_US |
Affilliation | Government Hospital of Thoracic Medicine. Chennai, India. | en_US |
Affilliation | Department of Clinical Research. National Institute for Research in Tuberculosis. Chennai, India. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Government Hospital of Thoracic Medicine. Chennai, India. | en_US |
Affilliation | Government Hospital of Thoracic Medicine. Chennai, India. | en_US |
Affilliation | HIV Pathogenesis Section. Laboratory of Immunoregulation. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD, United States. | en_US |
Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD, United States. | en_US |
Affilliation | Department of Clinical Research. National Institute for Research in Tuberculosis. Chennai, India. | en_US |
Affilliation | HIV Pathogenesis Section. Laboratory of Immunoregulation. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD, United States. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brazil/ Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil/Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brazil/Universidade Salvador. Curso de Medicina. Salvador, BA, Brazil/Federal do Rio de Janeiro. Programa de Pós-Graduação em Clínica Médica. Rio de Janeiro, RJ, Brazil/Wellcome Trust Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa/ Escola Bahiana de Medicina e Saúde Pública. Curso de MedicinaSalvador, BA, Brazil/ Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States. | en_US |
Subject | CD8+ T cells | en_US |
Subject | M. tuberculosis infection | en_US |
Subject | TB-IRIS | en_US |
Subject | immunologic memory | en_US |
Subject | naïve lymphocytes | en_US |